Material self-assembly method and selective adhesion method based on molecular recognition

ABSTRACT

The present invention provides a selective adhesion method and a self-assembly method for macroscale materials based on molecular recognition. One or more host bodies formed from a macromolecule having one or more host groups on the side chains, and one or more guest bodies formed from a macromolecule having one or more guest groups on the side chains are vibrated in a solvent to selectively form an assembly.

TECHNICAL FIELD

The present invention relates to a selective adhesion method and aself-assembly method for materials based on molecular recognition.

BACKGROUND ART

Though many reports are available on molecular self-assembly,self-assembly of components of an observable size (macroscaleself-assembly) is not well studied. There is a report of macroscaleself-assembly that involves, for example, magnetic interaction,electrical interaction, hydrophilic-lipophilic balance, and capillary(Non-Patent Literature 1). However, there is hardly any report ofself-assembly of macroscale materials based on molecular recognition.

CITATION LIST Non-Patent Literature

NPL 1: Whitesides, G. M. & Grzybowski, B., Self-assembly at all scale,Science, 295, 2418-2421 (2002)

SUMMARY OF INVENTION Technical Problem

It is an object of the present invention to provide a selective adhesionmethod and a self-assembly method for macroscale materials based onmolecular recognition.

Solution to Problem

The present inventors conducted intensive studies over the foregoingproblem, and found that an assembly can be formed when one or more hostbodies formed from a macromolecule having one or more host groups on theside chains, and one or more guest bodies formed from a macromoleculehaving one or more guest groups on the side chains are vibrated in asolvent. It was also found that the host body and the guest bodyselectively form an assembly by molecular recognition. The presentinvention was completed after further studies based on these findings.

Specifically, the present invention provides a selective adhesion methodand a self-assembly method for macroscale materials based on molecularrecognition, as follows.

Item 1

An assembly comprising one or more host bodies formed from amacromolecule having one or more host groups in the side chains, and oneor more guest bodies formed from a macromolecule having one or moreguest groups in the side chains, wherein the one or more host bodies andthe one or more guest bodies are in contact with each other and form theassembly.

Item 2

An assembly according to Item 1, wherein the association constantbetween the one or more host bodies and the one or more guest bodies is50 or more.

Item 3

An assembly according to Item 1 or 2, wherein the one or more hostbodies are a polymer having repeating units represented by the followinggeneral formulae (1) and (2)

wherein X represents a hydroxyl group, C(O)NH₂, or C(O)OH, and n is 1 to200,000,

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin,and m is 1 to 200,000.

Item 4

An assembly according to Item 3, wherein the one or more host bodies area copolymer of acrylamide and an acrylamide that has cyclodextrin on theside chain.

Item 5

An assembly according to Item 3 or 4, wherein the one or more hostbodies are a gel of a crosslinked polymer having repeating unitsrepresented by the general formulae (1) and (2).

Item 6

An assembly according to any one of Items 1 to 5, wherein the one ormore guest bodies are a polymer having repeating units represented bythe following general formulae (1) and (3)

wherein X represents a hydroxyl group, C(O)NH₂, or C(O)OH, and n is 1 to200,000,

wherein A represents O or NH, R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group, and l is 1 to200,000.

Item 7

An assembly according to Item 6, wherein the one or more guest bodiesare a copolymer of acrylamide and an acryl compound selected from thegroup consisting of an alkyl ester of acrylic acid, an aryl ester ofacrylic acid, and an acrylamide having a cycloalkyl group on the sidechain.

Item 8

An assembly according to Item 6 or 7, wherein the one or more guestbodies are a gel of a crosslinked polymer having the repeating unitsrepresented by the general formulae (1) and (3).

Item 9

A polymer that has one or more host groups and one or more guest groupson the side chains, and that has repeating units represented by thefollowing general formulae (2) and (3)

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin,and m is 1 to 200,000,

wherein A represents O or NH, R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group, and l is 1 to200,000.

Item 10

A gel formed by crosslinking of the polymer of Item 9.

Item 11

A method for selective adhesion of the gel of Item 10 through contact inan aqueous solvent.

Item 12

A method for causing one or more host bodies formed from a macromoleculehaving one or more host groups on the side chains, and one or more guestbodies formed from a macromolecule having one or more guest groups onthe side chains to selectively adhere to each other through contact inan aqueous solvent.

Advantageous Effects of Invention

The present invention enables selective adhesion of macroscale moleculesbased on molecular recognition. The invention also enables selectiveadhesion and self-assembly, and selective adhesion in water uponappropriately selecting host-guest molecules.

BRIEF DESCRIPTION OF DRAWINGS

The patent application file contains at least one drawing executed incolor. Copies of this patent or patent application with color drawingswill be provided by the Office upon request and payment of the necessaryfee.

FIG. 1 is an image showing how a β-CD-gel (host body gel) and an Ad-gel(guest body gel) adhere to each other and form a self-assembly.

FIG. 2 is an image showing how a β-CD-gel and an α-CD-gel (host bodygels) selectively adhere to an n-Bu-gel and a t-Bu-gel (guest body gels)and form self-assemblies.

FIG. 3 is a graph representing a stress-strain curve of an assemblyformed by the adhesion of a n-CD-gel (host body gel) and an Ad-gel(guest body gel).

DESCRIPTION OF EMBODIMENTS

The present invention is described below in detail.

1. Host Body

The host body of the present invention is formed from a macromoleculehaving one or more host groups on the side chains.

Examples of the host groups include artificial host molecules such asderivatives of cyclodextrin (CD), calixarene, crown ether, cyclophane,and cucurbituril. Specific examples include α-cyclodextrin,β-cyclodextrin, γ-cyclodextrin, calix[6]arene sulfonate, calix[8]arenesulfonate, 12-crown-4,18-crown-6, [6]paracyclophane,[2,2]paracyclophane, cucurbit[6]uril, and cucurbit[8]uril. Of these,α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin are preferred.

Examples of the macromolecules having one or more host groups on theside chains include polymers having the repeating units represented bythe foregoing general formulae (1) and (2). The number of repeatingunits (n, m) in the polymers having the repeating units represented bythe foregoing general formulae (1) and (2) is 1 to 200,000, preferably5,000 to 15,000.

The macromolecules having the repeating units represented by the generalformulae (1) and (2) may be produced by, for example, the reaction ofthe monomer of the following general formula (4) with the monomer of thegeneral formula (5) below.

wherein X represents a hydroxyl group, C(O)NH₂, or C(O)OH.

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin.

Any known monomer compounds may be used as the water-soluble monomersrepresented by the general formula (4). The monomer compounds may beused either alone or in a combination of two or more.

Particularly preferred as the monomer of the general formula (4) is thecompound in which X is C(O)NH₂, specifically, acrylamide.

The monomer represented by the general formula (5) is produced by thereaction of acryloyl chloride with 6-aminocyclodextrin. Typically,acryloyl chloride and 6-aminocyclodextrin are mixed and stirred in asolvent.

The reaction may be performed either solvent-free, or with a solvent (anorganic solvent or an aqueous solvent) commonly used in organicsynthesis reactions. Examples of the organic solvent includedimethylsulfoxide (DMSO), and dimethylformamide (DMF). Examples of theaqueous solvent include water, and buffers that contain salts such assodium phosphate and sodium carbonate as required. When used, the amountof the solvent may be appropriately adjusted.

The monomer of the general formula (5) may also be produced by using amethod in which 1,1′-carbonyldiimidazole (CDI) or1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehydrochloride (EDC) isadded to acrylic acid under ice-cooled conditions, and aminocyclodextrinis added to the mixture and stirred overnight to form an amide bond.Alternatively, the monomer of the general formula (5) may be produced byobtaining an amide compound from acrylic acid via an active ester, usingdicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) orN-hydroxysuccinimide (HOSu) as condensing agents.

The monomer of the general formula (5), and the known monomer of thegeneral formula (4) are reacted to produce the polymer having therepeating units of the general formulae (1) and (2). Preferably, thepolymer is obtained as a gel, by using a crosslinker.

Preferably, the polymer is a polymer gel containing the repeating unitof the general formula (1) in an amount of 90 to 99 mol %, and therepeating unit of the general formula (2) in an amount of 10 to 1 mol %,with 0.1 to 10% of the repeating units being crosslinked. Particularlypreferably, the repeating unit of the general formula (1) accounts for95 to 98 mol %, and the repeating unit of the general formula (2)accounts for 5 to 2 mol %, and 0.5 to 1% of the repeating units arecrosslinked.

Further, the polymer preferably contains cyclodextrin in a proportion of1.0 to 5.0 mol %, particularly preferably 2.0 to 5.0 mol % with respectto the whole polymer having the repeating units of the general formulae(1) and (2).

The following describes a specific producing process of the polymer gelhaving the repeating units of the general formulae (1) and (2).

The polymer having the repeating units of the general formulae (1) and(2) is produced by the radical polymerization of the monomers of thegeneral formulas (4) and (5) with a crosslinker. Typically, the monomersof the general formulae (4) and (5), a crosslinker, and, optionally, aradical polymerization initiator are mixed and stirred in a vesselflushed with inert gas, or in a vacuum-deaerated vessel.

The radical polymerization reaction may be performed eithersolvent-free, or with a solvent (an organic solvent or an aqueoussolvent) commonly used in radical polymerization. Examples of theorganic solvent include benzene, toluene, N,N-dimethylformamide (DMF),dimethylsulfoxide (DMSO), acetone, chloroform, carbon tetrachloride,tetrahydrofuran (THF), ethyl acetate, chlorobenzene, dichlorobenzene,trifluoromethylbenzene, and anisole. Examples of the aqueous solventinclude water, and solvents that contain, for example, methanol,ethanol, isopropanol, n-butanol, ethyl cellosolve, butyl cellosolve, and1-methoxy-2-propanol, as required.

When used, the amount of the solvent may be appropriately adjusted. Forexample, the solvent is typically used in 0.1 to 1 liter, preferably 0.2to 0.5 liters with respect to the total amount 1 mole of the monomersused for the polymerization.

The crosslinker may be any known crosslinker. For example,N,N′-methylene-bisacrylamide is preferably used.

The radical polymerization reaction may be performed in the presence orabsence of a radical polymerization initiator. Typically, the radicalpolymerization reaction is preferably performed in the presence of aradical polymerization initiator. The radical polymerization reactionmay involve spontaneous thermal polymerization in the absence of aradical polymerization initiator, or photoirradiation in the presence orabsence of a radical polymerization initiator. In the case ofphotoirradiation radical polymerization, a light source such as amercury lamp or a xenon lamp is typically used for the polymerization.The light source may be appropriately selected taking into considerationfactors such as the type of the vinyl monomer, and the type of thepolymerization initiator used.

2. Guest Body

The guest body of the present invention is formed from a macromoleculehaving one or more guest groups on the side chains.

The guest group may be any group that can be a guest group for acorresponding host group. Examples include alkyl groups that may have asubstituent or substituents, cycloalkyl groups, and aryl groups that mayhave a substituent or substituents.

Examples of the macromolecules having one or more guest groups on theside chains include polymers having the repeating units represented bythe general formulae (1) and (3). The number of repeating units (n, l)in the polymers represented by the general formulae (1) and (3) is 1 to200,000, preferably 5,000 to 15,000.

The polymers having the repeating units represented by the generalformulae (1) and (3) can be produced by, for example, the reaction ofthe monomer of the following general formula (4) with the monomer of thegeneral formula (6) below.

wherein X represents a hydroxyl group, C(O)NH₂, or C(O)OH.

wherein A represents O or NH, and R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group.

Any known monomer compounds may be used as the water-soluble monomersrepresented by the general formula (4). The monomer compounds may beused either alone or in a combination of two or more. It is particularlypreferable to use the same monomer compounds used for the host body.

Particularly preferred as the monomer of the general formula (4) is thecompound in which X is C(O)NH₂, specifically, acrylamide.

Examples of the alkyl groups, which may be optionally substituted,represented by R in the general formula (6) include linear, branched, orcyclic alkyl groups of C1 to C18. Specific examples include alkyls suchas methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, pentyl, cyclopentyl, hexyl, cyclohexyl, isohexyl, dodecyl,octadecyl, and adamantyl. Of these, adamantyl and butyl are preferred,and adamantyl is particularly preferred. The alkyl group may have 1 to 3substituents, for example, such as halogen atoms (for example, such asfluorine, chlorine, and bromine), carboxyl groups, ester groups, amidegroups, and hydroxyl groups that may be protected. Further, the alkylgroup may be one in which the organometal complex ferrocene is attachedas a substituent.

Examples of the aryl groups, which may be optionally substituted,represented by R in the general formula (6) include monocyclic arylgroups, and aryl groups with two or more rings. Specific examplesinclude phenyl, toluoyl, xylyl, naphthyl, anthryl, and phenanthryl. Thearyl group may have 1 to 3 substituents, for example, such as alkylgroups (for example, such as C1 to C18 alkyl groups), halogen atoms (forexample, such as fluorine, chlorine, and bromine), carboxyl groups,ester groups, amide groups, azo groups having aryl groups, and hydroxylgroups that may be protected.

The monomer of the general formula (6) is produced by the reaction ofacryloyl chloride with an alkyl amine or an aryl amine that provides analkyl or an aryl for the substituent R. Typically, acryloyl chloride ismixed and stirred in a solvent with an alkyl amine or an aryl amine thatprovides an alkyl or an aryl for the substituent R.

The same solvent used for the production of the monomer of the generalformula (5) may be used in the reaction. When used, the amount of thesolvent may be appropriately adjusted.

The monomer of the general formula (6) may also be produced by using amethod in which 1,1′-carbonyldiimidazole (CDI) or1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehydrochloride (EDC) isadded to acrylic acid under ice-cooled conditions, and aminocyclodextrinis added to the mixture and stirred overnight to form an amide bond.Alternatively, the monomer of the general formula (6) may be produced byobtaining an amide compound from acrylic acid via an active ester, usingdicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) orN-hydroxysuccinimide (HOSu) as condensing agents.

The monomer of the general formula (6), and the known monomer of thegeneral formula (4) are reacted to produce the polymer having therepeating units of the general formulae (1) and (3). Preferably, thepolymer is obtained as a gel, by using a crosslinker.

Preferably, the polymer is a polymer gel containing the repeating unitof the general formula (1) in an amount of 90 to 99 mol %, and therepeating unit of the general formula (3) in an amount of 10 to 1 mol %,with 0.1 to 10% of the repeating units being crosslinked. Particularlypreferably, the repeating unit of the general formula (1) accounts for95 to 98 mol %, and the repeating unit of the general formula (3)accounts for 5 to 2 mol %, and 0.5 to 1% of the repeating units arecrosslinked.

Further, the polymer gel preferably contains the guest group in aproportion of 1.0 to 5.0 mol %, particularly preferably 2.0 to 5.0 mol %with respect to the whole polymer having the repeating units of thegeneral formulae (1) and (3).

The polymer gel having the repeating units of the general formulae (1)and (3) is produced by using the same process used to produce thepolymer gel having the repeating units of the general formulae (1) and(2).

3. Polymer Having Host Group and Guest Group

In the present invention, the polymer having one or more host groups andone or more guest groups on the side chains is a polymer having therepeating units of the following general formulae (2) and (3)

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin,and m is 1 to 200,000.

wherein A represents O or NH, R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group, and l is 1 to200,000.

The number of repeating units (m, l) in the polymer having the repeatingunits of the general formulae (2) and (3) is 1 to 200,000, preferably5,000 to 15,000.

The polymer having the repeating units of the general formulae (2) and(3) may be produced, for example, by the reaction of the monomer of thegeneral formula (5) described in Section 1. above with the monomer ofthe general formula (6) described in Section 2.

In the reaction, the monomer of the general formula (4) may be furtherpolymerized. Preferably, the polymer is obtained as a gel, by using acrosslinker.

Preferably, the polymer is a polymer gel containing the repeating unitof the general formula (2) in an amount of 40 to 60 mol %, and therepeating unit of the general formula (3) in an amount of 60 to 40 mol%, with 0.1 to 10% of the repeating units being crosslinked.Particularly preferably, the repeating unit of the general formula (2)accounts for 50 mol %, and the repeating unit of the general formula (3)accounts for 50 mol %, and 0.5 to 1% of the repeating units arecrosslinked.

Further, the polymer gel preferably contains the one or more host groupsin a proportion of 40 to 60 mol %, particularly preferably 50 mol %, andthe guest group in a proportion of 60 to 40 mol %, particularlypreferably 50 mol % with respect to the whole polymer having therepeating units of the general formulae (2) and (3).

The polymer gel having the repeating units of the general formulae (2)and (3) is produced by using the same process used to produce thepolymer gel having the repeating units of the general formulae (1) and(2).

4. Assembly

The assembly of the present invention is obtained by bringing intocontact (i) the host body and the guest body, (ii) the polymers havingthe host group and the guest group on the side chains, (iii) the hostbody and the polymer having the host group and the guest group on theside chains, and (iv) the guest body and the polymer having the hostgroup and the guest group on the side chains.

Particularly preferably, the assembly of the present invention can beobtained by bringing into contact the host body, the guest body, and thepolymer having the host group and the guest group on the side chains ingel form in an aqueous solvent.

Specifically, by taking the contact between the host body and the guestbody as an example, a host body gel and a guest body gel are placed inan aqueous solvent, and brought into contact with each other undervibration or stirring.

Examples of the aqueous solvent include water, aqueous solutions thatcontain salts such as sodium phosphate and sodium carbonate as required,and mixed solvents of, for example, alcohol and water. The aqueoussolvent is preferably water.

Any means can be used as the vibration or stirring method, as long asthe host body and the guest body can be brought close to each otherwithin a certain distance. Examples include methods that use a stirreror a shaking machine such as a vortex mixer and a shaker, and methodsthat irradiate ultrasonic waves.

The same solvent, and the same vibration or stirring method may be usedfor the polymer having the host group and the guest group on the sidechains.

As used herein, the term assembly is used to refer to a form in whichthe host body and the guest body, or the polymers having the host groupand the guest group on the side chains contact and adhere to each otheron their surfaces.

The assembly of the present invention occurs, for example, as the hostbody and the guest body are brought close to each other within a certaindistance, and attract and adhere to each other over the adjacentsurfaces. In the present invention, the adhesion between the host bodyand the guest body is selective as determined by the combination of thehost body and the guest body. Likewise, the adhesion between thepolymers having the host group and the guest group on the side chains isalso selective as determined by the combination of the host group andthe guest group. Specifically, the adhesion is based on molecularrecognition, and the certain distance and the attraction force by whichthe host body (group) and the guest body (group) attract each other isdetermined by the combination of the host body (group) and the guestbody (group).

Adhesion occurs when the guest body (group) has a size that can beaccommodated by the internal space of the host body (group), and whenthe guest body (group) has interactions with the host body (group)(interactions that involve at least one of hydrophobic interaction (Vander Waals force), hydrogen bonding, electrostatic interaction, andcoordinate bonding).

The selectivity is believed to involve association constant (K).

Here, association constant (K) is a value determined from NMR peakshifts by using the Benesi-Hildebrand method, as described below indetail.

Cyclodextrin is added to a guest molecule of a certain concentration(the concentration of the guest sites in the monomer or polymer is heldconstant), and a signal shift originating in the guest sites ismeasured. When the signal shift amount is Δδ, (and when the maximumshift amount (the shift amount of when the cyclodextrin binds to all theguest sites) is Δδmax), the association constant K is calculated asfollows.1/Δδ=(1/KΔδmax)·(1/[cyclodextrin])+1/Δδmax  Equation:

Here, Δδmax can be calculated from the ordinate intercept, and K fromthe slope (and the Δδmax determined first) by plotting 1/Δδ and1/[cyclodextrin] against the vertical axis and the horizontal axis (adouble reciprocal plot of Δδ and [cyclodextrin]).

In the assembly of the present invention, the association constantbetween the host body (group) and the guest body (group) is preferablyabout 50 or more.

For example, when α-cyclodextrin (cavity size: 4.7 to 5.2 Å) is used asthe host body (group), examples of the guest body (group) that satisfiesthe foregoing conditions include alkyl compounds of 4 to 18 carbonatoms, alcohol derivatives thereof, carboxylic acid derivatives, aminoderivatives, azobenzene derivatives having a cyclic alkyl group or aphenyl group, and cinnamic acid derivatives. Examples of the alkylcompounds (groups) of 4 to 18 carbon atoms include n-butyl, pentyl,hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl,tetradecyl, pentadecyl, hexadecyl, heptadecyl, and octadecyl.

When β-cyclodextrin (cavity size: 6.0 to 6.5 Å) is used, examples of theguest body (group) that satisfies the foregoing conditions includet-butyl, adamantyl, aromatic compounds and alcohol derivatives thereof,carboxylic acid derivatives, amino derivatives, ferrocene derivatives,azobenzene, naphthalene derivatives, and dansyl.

When γ-cyclodextrin (cavity size: 7.5 to 8.5 Å) is used, examples of theguest body (group) that satisfies the foregoing conditions include alkylof up to 18 carbon atoms, alcohol derivatives thereof, carboxylic acidderivatives, amino derivatives, adamantyl, clusters of carbon atoms(such as fullerene), aromatic dansyl, ferrocene derivatives, andanthracene derivatives.

The break strength of the assembly tends to increase as the associationconstant between the host body and the guest body increases. Preferably,the assembly has a break strength of 200 to 1,000 kPa, and a fractureelongation of 10 to 90%.

The polymers having the host group and the guest group on the sidechains adhere in the same manner as in the adhesion of the host body andthe guest body. The polymer gel having the host group and the guestgroup on the side chains can remain adherent even when cut, because anycut in the gel exposes the host group and the guest group.

The present invention enables selective adhesion of macroscale materialsbased on molecular recognition. Further, the present invention enablesselective adhesion and self-assembly, and selective adhesion in waterupon appropriately selecting host-guest molecules.

Because the present invention enables selective adhesion of macroscalematerials based on host-guest molecular recognition, selective adhesionand self-assembly can take place at an adhesion strength that can beadjusted by appropriately selecting host-guest molecules. The presentinvention also enables selective adhesion in water.

Thus, by taking advantage of the selectivity, the selective adhesion andself-assembly based on molecular recognition of the present inventionhas applications, for example, such as in cell and tissue fixingmaterial, organ adhesion inhibiting material, alternative suturematerial, and DDS material. Further, because the adhesion andself-assembly occurs at macroscale, the invention is also applicable to,for example, sensor materials. Further, because the adhesion can takeplace in a gel state, the invention has potential application in plasticprocessing techniques that involve drying of the adhered product forproduction of small and hard assemblies.

EXAMPLES

The present invention is described below in greater detail usingExamples. It should be noted, however, that the invention is not limitedby the descriptions of the following Examples.

Measurement Devices

The following devices were used for the measurements of variousproperties in the Examples and Comparative Examples.

¹H-NMR: JEOL ECA-500 (500 MHz)

MS: Shimadzu Corporation AXIMA-CFR (time-of-flight)

Elemental analysis: Yanaco, CHNCORDER MT-6 (differential thermalconductivity method)

Break strength and elongation: Rhenoner, RE-33005, Yamaden Ltd. (testpiece: 1 cm×1 cm; pulling rate: 0.1 mm/sec; measurement temperature:room temperature)

Production of Host Body Polymerization Monomer

Production Example 1 6-acrylamide-α-cyclodextrin

6-Amino-α-cyclodextrin (0.58 g; 0.60 mmol) was dissolved in a 50-mlNaHCO₃ aqueous solution (0.5 g), and the pH of the solution was broughtto about 10 with NaOH. Acryloyl chloride (90 μl; 1.2 mmol) was added tothe 6-amino-α-cyclodextrin solution on an ice bath, and the mixture wasstirred for 6 hours. After the reaction, the mixture was concentrated toabout 50% of the total amount, and poured into acetone (500 mL).Thereafter, the precipitate was collected by centrifugation, and driedovernight in a vacuum oven. The resulting crude product was generated byreversed-phase chromatography with HP-20 polystyrene gel(methanol/water) to give 6-acrylamide-α-cyclodextrin (0.49 g; yield:79%).

¹H-NMR (DMSO-d₆): δ8.00 (t, 1H, amido), 6.27 (dd, 1H, olefin), 6.02 (d,1H, olefin), 5.58-5.34 (d, 1H, olefin, m, 13H, O₂, ₃H of CD), 4.89-4.74(m, 6H, C₁H of CD), 4.54-4.38 (m, 5H, O₆H of CD), 3.84-3.20 (m, overlapswith HOD)

MALDI-TOF MS; m/z=1025.3 ([C₃₉H₆₃NO₃₀+Na]+=1048.3)[C₃₉H₆₃NO₃₀+K]+=1064.4)

Elemental analysis (C₃₉H₆₃NO₃₀ (H₂O)₆): C, 41.31; H, 6.67; N, 1.24.

Measurement result: C, 41.24; H, 6.36; N, 1.30.

Production Example 2 6-acrylamide-β-cyclodextrin

6-Amino-β-cyclodextrin (0.68 g; 0.60 mmol) was dissolved in a 50-mlNaHCO₃ aqueous solution (0.5 g), and the pH of the solution was broughtto about 10 with NaOH. Acryloyl chloride (90 μl; 1.2 mmol) was added tothe 6-amino-β-cyclodextrin solution on an ice bath, and the mixture wasstirred for 6 hours. After the reaction, the mixture was concentrated to10% of the total amount, and poured into acetone (500 mL). Thereafter,the precipitate was collected by centrifugation, and dried overnight ina vacuum oven. The resulting crude product was generated byreversed-phase chromatography with HP-20 polystyrene gel(methanol/water) to give 6-acrylamide-β-cyclodextrin (0.53 g; yield:74%).

¹H-NMR (DMSO-d₆): δ7.90 (t, 1H, amido), 6.27 (dd, 1H, olefin), 6.02 (d,1H, olefin), 5.90-5.60 (d, 1H, olefin, m, 15H, O₂, ₃H of CD), 4.89-4.74(m, 7H, C₁H of CD), 4.54-4.38 (m, 6H, O₆H of CD), 3.84-3.20 (m, overlapswith HOD)

MALDI-TOF MS; m/z=1208.0 ([C₄₅H₇₃NO₃₅+Na]+=1210.4), 1223.8([C₄₅H₇₃NO₃₅+K]+=1226.5)

Elemental analysis (C₄₅H₇₃NO₃₅(H₂O)_(3.32)): C, 41.54; H, 6.17; N, 1.07.

Measurement result: C, 41.54; H, 6.37; N, 1.16.

Production of Guest Body Polymerization Monomer

Production Example 3 N-(1-adamantyl)acrylamide

1-Adamantylamine (0.76 g; 5.0 mmol) and triethylamine (0.77 ml; 5.5mmol) were dissolved in dry THF (40 mL) on an ice bath. After droppingacryloyl chloride (0.45 ml; 5.5 mmol) onto the solution, the mixture wasstirred for 4 hours. After the reaction, the precipitate was removed byfiltration, and the supernatant liquid was concentrated under reducedpressure. The resulting crude product was recrystallized from chloroformto give N-(1-adamantyl)acrylamide (0.85 mg; yield: 83%).

¹H-NMR ((CD₃)SO): δ6.15 (dd, 1H, olefin), 5.96 (dd, 1H, olefin), 5.56(dd, 1H, olefin), 5.56 (dd, 1H, olefin), 5.15 (brs, 1H, NH), 2.06 (m,9H, adamantine), 1.59 (m, 6H, adamantine)

MALDI-TOF MS; m/z=228.6 ([C₁₃H₁₉NO+Na]+=228.1) [C₃₉H₆₃NO₃₀+K]+=244.4)

Elemental analysis (C₁₃H₁₉NO(H₂O)_(0.16)): C, 74.09; H, 9.24; N, 6.64.

Measurement result: C, 74.06; H, 9.18; N, 6.61.

Production of Host Body Macromolecule

Polymerization Example 1

The 6-acrylamide-β-cyclodextrin (6.8 mmol) obtained in ProductionExample 2, and acrylamide (340 mmol) were subjected to a radicalpolymerization reaction in water, using ammonium persulfate (APS; 0.006mmol) and N,N,N′,N′-tetramethylethylenediamine (TMEDA; 0.006 mmol) asinitiators. After 12 hours of reaction, the unreactant was removed bydialysis. The resulting solution was concentrated under reduced pressureto give a host macromolecule (yield 87%).

¹H NMR (500 MHz, D₂O): δ5.20-5.10 (m, 7H, C₁H of CD), 4.10-3.60 (m, 42H,C_(2,3,4,5,6)H of CD), 2.50-2.10 (methine proton of the polymer mainchain), 2.00-1.50 (methylene proton of the polymer main chain).

Polymerization Example 2

A host macromolecule (yield 83%) was obtained in the same manner as inPolymerization Example 1, except that the 6-acrylamide-α-CD obtained inProduction Example 1 was used in place of the 6-acrylamide-β-CD.

¹H NMR (500 MHz, D₂O): δ5.20-5.10 (m, 6H, C₁H of CD), 4.10-3.60 (m, 36H,C_(2,3,4,5,6)H of CD), 2.50-2.10 (methine proton of the polymer mainchain), 2.00-1.45 (methylene proton of the polymer main chain).

Production of Guest Body Macromolecule

Polymerization Example 3

The N-(1-Ad)acrylamide (0.62 mmol) obtained in Production Example 3, andacrylamide (31 mmol) were subjected to a radical polymerization reactionin dimethylsulfoxide (DMSO; 30 ml) at 60° C., using2,2′-azobis(isobutyronitrile) (AIBN; 0.04 mmol).

After 12 hours of reaction, the mixture was reprecipitated withmethanbl, and dried under reduced pressure to obtain a crude product.This procedure was repeated three times to produce a guest macromolecule(yield 93%).

¹H NMR (500 MHz, D₂O): δ2.50-1.95 (methine proton of the polymer mainchain, adamantane proton), 1.95-1.40 (methylene proton of the polymermain chain, adamantane proton).

Production of Host Body Gel

Crosslink Example 1

The 6-acrylamide-β-CD (0.31 mmol) obtained in Production Example 2,acrylamide (6.2 mmol), and N,N′-methylenebis(acrylamide) (0.03 mmol)were subjected to a radical polymerization reaction in water to obtain ahost body gel, using APS (0.0013 mmol) and TMEDA (0.0052 mmol) asinitiators.

Crosslink Example 2

A host body gel was obtained in the same manner as in Crosslink Example1, except that the 6-acrylamide-α-CD obtained in Production Example 1was used in place of the 6-acrylamide-β-CD.

Production of Guest Body Gel

Crosslink Example 3

The N-(1-Ad)acrylamide (0.32 mmol) obtained in Production Example 3,acrylamide (6.2 mmol), and N,N′-methylenebis(acrylamide) (0.12 mmol)were subjected to a radical polymerization reaction in DMSO (3.5 ml) at63° C., using AIBN (0.03 mmol). After 12 hours of reaction, the solventin the gel was displaced with water in repeating fashion to obtain aguest body gel.

Crosslink Example 4

A guest body gel was obtained in the same manner as in Crosslink Example3, except that n-butyl acrylate (Tokyo Chemical Industry Co., Ltd.) wasused in place of the N-(1-Ad) acrylamide.

Crosslink Example 5

A guest body gel was obtained in the same manner as in Crosslink Example3, except that t-butyl acrylate (Tokyo Chemical Industry Co., Ltd.) wasused in place of the N-(1-Ad) acrylamide.

Contacting of Gels

The Gels obtained in Crosslink Examples 1 to 5 were each cut into a cubemeasuring 3 mm×3 mm×3 mm.

For the visual inspection of assembly formation, the gel having β-CDobtained in Crosslink Example 1 was dyed red by being dipped in a reddye (erythrosine, red 3) solution.

In the same manner, the gel having α-CD obtained in Crosslink Example 2was dyed blue (brilliant blue, blue 1), the gel having Ad obtained inCrosslink Example 3 was dyed pale green (malachite green, or a mixtureof low-concentration blue 1 and yellow 4), the gel having n-Bu groupobtained in Crosslink Example 4 was dyed yellow (tartrazine, yellow 4),and the gel having t-Bu group obtained in Crosslink Example 5 was dyedgreen (a mixture of blue 1 and yellow 4).

Example 1

The gel having the host group β-CD (Crosslink Example 1), and the gelhaving the guest group Ad (Crosslink Example 3) were placed in a petridish, and vibrated at room temperature for several minutes with EYELACM-1000 after adding water (5 mL).

As shown in FIG. 1, the β-CD-containing host body gel and theAd-containing guest body gel attracted each other when brought close toeach other, and strongly adhered to each other and formed an assembly.

The assembly was measured for fracture elongation and break strength.The resulting stress-strain curve is represented in FIG. 3. Themeasurement results are presented in Table 1.

Example 2

The gel having the host group α-CD (Crosslink Example 2), and the gelhaving the guest group Ad (Crosslink Example 3) were placed in a petridish, and vibrated at room temperature for several minutes with EYELACM-1000 after adding water (5 mL).

The α-CD-containing host body gel and the Ad-containing guest body gelattracted each other when brought close to each other, and adhered toeach other and formed an assembly.

The assembly was measured for fracture elongation and break strength.The results are presented in Table 1.

Example 3

The gel having the host group β-CD (Crosslink Example 1), the gel havingthe host group α-CD (Crosslink Example 2), the gel having the guestgroup n-Bu (Crosslink Example 4), and the gel having the guest groupt-Bu (Crosslink Example 5) were placed in a petri dish, and vibrated atroom temperature for several minutes with EYELA CM-1000 after addingwater (5 mL).

As shown in FIG. 2, the β-CD-containing host body gel did not adhere tothe n-Bu group-containing guest body gel, and selectively formed anassembly only with the t-Bu group-containing guest body gel. Theα-CD-containing host body gel did not adhere to the t-Bugroup-containing guest body gel, and selectively formed an assembly onlywith the n-Bu group-containing guest body gel.

The assemblies were measured for fracture elongation and break strength.The results are presented in Table 1.

TABLE 1 Break Fracture Association Guest Ad- strength elongationconstant Host gel gel hesion^(a) (kPa) (%) (Ka/M⁻¹)^(b) Ex. 1 β-CD-gelAd-gel Excel- 900 85 1,500 lent Ex. 2 α-CD-gel Ad-gel Good 750 65 98 Ex.3 α-CD-gel n-Bu- Good 200 15 57 gel α-CD-gel t-Bu-gel Poor — — ≈15β-CD-gel n-Bu- Poor — — <10 gel β-CD-gel t-Bu-gel Good 700 18 170^(a)Excellent means strong adhesion; Good means adhesion; Poor means noadhesion ^(b)Calculated from ¹H NMR according to Benesi-Hildebrandmethod

It can be seen from the results presented in Table 1 that the assemblieswith larger association constants have larger break strengths.

The invention claimed is:
 1. An assembly comprising one or more hostbodies formed from a macromolecule having one or more host groups in theside chains, and one or more guest bodies formed from a macromoleculehaving one or more guest groups in the side chains, wherein the one ormore host bodies and the one or more guest bodies are in contact witheach other and form the assembly, wherein the one or more host bodiesare a gel of a crosslinked polymer having repeating units represented bythe following general formulae (1) and (2), and the one or more guestbodies are a gel of a crosslinked polymer having repeating unitsrepresented by the following general formulae (1) and (3):

wherein X represents a hydroxyl group, C(O)NH₂, or C(O)OH, and n is 1 to200,000,

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin,and m is 1 to 200,000,

wherein A represents O or NH, R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group, and l is 1 to200,000, the host groups corresponding to the group CD in generalformula (2), and the guest groups corresponding to the group R ingeneral formula (3).
 2. An assembly according to claim 1, wherein theassociation constant between the one or more host bodies and the one ormore guest bodies is 50 or more.
 3. An assembly according to claim 1,wherein the one or more host bodies are a copolymer of acrylamide and anacrylamide that has cyclodextrin on the side chain.
 4. An assemblyaccording to claim 1, wherein the one or more guest bodies are acopolymer of acrylamide and an acryl compound selected from the groupconsisting of an alkyl ester of acrylic acid, an aryl ester of acrylicacid, and an acrylamide having a cycloalkyl group on the side chain. 5.A method for causing one or more host bodies formed from a macromoleculehaving one or more host groups on the side chains, and one or more guestbodies formed from a macromolecule having one or more guest groups onthe side chains to selectively adhere to each other through contact inan aqueous solvent, the method comprising the step of contacting themacromolecule having one or more host groups on the side chains with themacromolecule having one or more guest groups on the side chain, whereinthe one or more host bodies are a gel of a crosslinked polymer havingrepeating units represented by the following general formulae (1) and(2), and the one or more guest bodies are a gel of a crosslinked polymerhaving repeating units represented by the following general formulae (1)and (3):

wherein X represents a hydroxyl group, C(O)NH₂, or C(0)OH, and n is 1 to200,000,

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin,and m is 1 to 200,000,

wherein A represents O or NH, R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group, and l is 1 to200,000, the host groups corresponding to the group CD in generalformula (2), and the guest groups corresponding to the group R ingeneral formula (3).
 6. An assembly according to claim 1, wherein theone or more host bodies are a gel of a crosslinked polymer havingrepeating units represented by the following general formulae (1), (2)and (3), and the one or more guest bodies are a gel of a crosslinkedpolymer having repeating units represented by the following generalformulae (1), (2) and (3):

wherein X represents a hydroxyl group, C(O)NH₂, or C(O)OH, and n is 1 to200,000,

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin,and m is 1 to 200,000,

wherein A represents 0 or NH, R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group, and l is 1 to200,000, the host groups corresponding to the group CD in generalformula (2), and the guest groups corresponding to the group R ingeneral formula (3).
 7. A method for causing one or more host bodiesformed from a macromolecule having one or more host groups on the sidechains, and one or more guest bodies formed from a macromolecule havingone or more guest groups on the side chains to selectively adhere toeach other through contact in an aqueous solvent, the method comprisingthe step of contacting the macromolecule having one or more host groupson the side chains with the macromolecule having one or more guestgroups on the side chain, wherein the one or more host bodies are a gelof a crosslinked polymer having repeating units represented by thefollowing general formulae (1), (2) and(3), and the one or more guestbodies are a gel of a crosslinked polymer having repeating unitsrepresented by the following general formulae (1), (2) and (3):

wherein X represents a hydroxyl group, C(O)NH₂, or C(O)OH, and n is 1 to200,000,

wherein CD represents α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin,and m is 1 to 200,000,

wherein A represents O or NH, R represents an optionally-substitutedalkyl group, or an optionally-substituted aryl group, and l is 1 to200,000, the host groups corresponding to the group CD in generalformula (2), and the guest groups corresponding to the group R ingeneral formula (3).
 8. A method according to claim 7, wherein thecontact between the one or more host bodies and the one or more guestbodies is re-contact made after the assembly is cut.